Amyloid β-protein suppressed nicotinic acetylcholine receptor-mediated currents in acutely isolated rat hippocampal CA1 pyramidal neurons
Article first published online: 16 OCT 2012
Copyright © 2012 Wiley Periodicals, Inc.
Volume 67, Issue 1, pages 11–20, January 2013
How to Cite
He, Y.-X., Wu, M.-N., Zhang, H. and Qi, J.-S. (2013), Amyloid β-protein suppressed nicotinic acetylcholine receptor-mediated currents in acutely isolated rat hippocampal CA1 pyramidal neurons. Synapse, 67: 11–20. doi: 10.1002/syn.21611
- Issue published online: 27 NOV 2012
- Article first published online: 16 OCT 2012
- Accepted manuscript online: 26 SEP 2012 06:56AM EST
- Manuscript Accepted: 14 SEP 2012
- Manuscript Received: 10 JUL 2012
- Natural Science Foundation of Shanxi Province, China. Grant Number: 2010011049-3
- The Shanxi Province Science Foundation for Youth. Grant Number: 2011021036-2
- The Dean's fund of Key Laboratory of Cellular Physiology, Ministry of Education, Shanxi Medical University. Grant Number: 201008
- The Scientific Research Foundation of the Higher Education Institutions of Shanxi Province, China. Grant Number: 20091111.
- whole-cell patch clamp;
Amyloid β protein (Aβ) is responsible for the deficits of learning and memory in Alzheimer's disease (AD). The high affinity between Aβ and nicotinic acetylcholine receptors (nAChRs) suggests that the impairment of cognitive function in AD might be involved in the Aβ-induced damage of nAChRs. This study investigated the effects of Aβ fragments on nAChR-mediated membrane currents in acutely isolated rat hippocampal pyramidal neurons by using whole-cell patch clamp technique. The results showed that: (1) nonspecific nAChR agonist nicotine, selective α7 nAChR agonist choline, and α4β2 nAChR agonist epibatidine all effectively evoked inward currents in CA1 neurons at normal resting membrane potential, with different desensitization characteristics; (2) acute application of different concentrations (pM–μM) of Aβ25-35, Aβ31-35, or Aβ35-31 alone did not trigger any membrane current, but pretreatment with 1 μM Aβ25-35 and Aβ31-35 similarly and reversibly suppressed the nicotine-induced currents; (3) further, choline- and epibatidine-induced currents were also reversibly suppressed by the Aβ pretreatment, but more prominent for the choline-induced response. These results demonstrate that the functional activity of both α7 and α4β2 nAChRs in the membrane of acutely isolated hippocampal neurons was significantly downregulated by Aβ treatment, suggesting that nAChRs, especially α7 nAChRs, in the brain may be the important biological targets of neurotoxic Aβ in AD. In addition, the similar suppression of nAChR currents by Aβ25-35 and Aβ31-35 suggests that the sequence 31-35 in Aβ molecule may be a shorter active center responsible for the neurotoxicity of Aβ in AD. Synapse, 2013. © 2012 Wiley Periodicals, Inc.